Insulin

A hormone secreted by the beta cells of the pancreas to help move glucose from the blood into body cells for energy. People with Type 1 diabetes lose the ability to produce insulin and must inject it. Some people with Type 2 diabetes also need to inject insulin because the insulin that is produced by their pancreas does not adequately lower their blood glucose level.

Scientists discovered insulin in the early 1920’s and found that it could be used to successfully treat diabetes. Since then, a variety of insulins have been developed to meet the different needs of people with diabetes.

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In the past, all commercially available insulin came from the pancreases of cows or pigs. Pork and beef insulins are similar to human insulin, differing only in one or a few amino acids (protein building blocks). However, even a slight difference is enough to elicit an allergic response in some people. To overcome this problem, researchers looked for ways to make insulin that would more closely resemble human insulin.

Since the early 1980’s, two methods have been used to make human insulin from nonhuman sources. One method involves the use of enzymes to convert pork insulin into human insulin by altering the one amino acid that is different. The second and more widely used method uses recombinant DNA technology. In this process, bacteria or yeast cells are genetically altered to produce human insulin in large amounts. Human insulin produced by genetic engineering is purer than other forms of insulin because it is not combined with other proteins that can also trigger allergic responses. Pork and beef insulin are no longer being sold in the United States.

In addition to originating from different sources, different types of insulin vary in their “action profile.” That’s to say, they differ in how quickly they begin to take effect, the point at which they reach peak effectiveness, and how long they continue to lower blood glucose. Regular insulin, which is a short-acting insulin, begins acting about 30 minutes after injection, peaks after 2 to 3 hours, and lasts for 6 to 8 hours. The intermediate-acting insulin NPH consists of Regular insulin and buffers that slow down the absorption of Regular insulin. This insulin starts to work in about 1 to 2 hours, peaks after 6 to 10 hours, and lasts about 16 to 24 hours.

One of the latest advances in insulin therapy is the development of insulin analogs. There are now two types of insulin analogs on the market: rapid-acting and long-acting. Rapid-acting analogs are modified forms of human insulin that have been altered in such a way that the molecules do not clump together the way Regular insulin molecules do. This allows them to be absorbed much more quickly into the bloodstream and to begin working, peak, and break down more quickly than Regular insulin. The first rapid-acting analog to come on the market was lispro (brand name Humalog) by Eli Lilly and Company, which was approved in 1996. A second rapid-acting insulin analog, aspart (NovoLog), made by Novo Nordisk, was approved in 2000, and a third, glulisine (Apidra), made by Sanofi-aventis, was approved in 2004.

The long-acting insulin analogs are glargine (Lantus), made by Sanofi-aventis and approved in 2000, and detemir (Levemir), made by Novo Nordisk and approved in 2005. These analogs are designed to be absorbed very slowly into the bloodstream, so that their effects last for 24 hours without peaking.

In addition to Regular, NPH, lispro, aspart, glulisine, glargine, and detemir, insulin is also sold in premixed combinations of NPH and Regular. It is packaged in the ratio of 70% NPH to 30% Regular. Eli Lilly also makes a combination product that’s 75% intermediate-acting insulin and 25% lispro, as well as one that’s 50% intermediate-acting insulin and 50% lispro, while Novo Nordisk makes a combination of 70% intermediate-acting insulin and 30% aspart.

All insulin regimens are made up of some combination of these different types of insulin. Some people can effectively manage their blood glucose levels with one or two injections of premixed insulin per day. These people must inject at specific times of the day, and also eat their meals at specific times. The shorter-acting insulin covers mealtimes and the longer-acting insulin maintains a steady amount of insulin in the bloodstream between meals. Some people with Type 2 diabetes manage their blood glucose levels by combining diabetes pills with one injection of longer-acting insulin in the evening or at bedtime.

Other people inject insulin several times a day, a practice that allows greater flexibility in the timing of their meals. Multiple injection regimens generally involve taking a shot of short-acting insulin before each meal, in combination with one or two injections of longer-acting insulin in the morning or at bedtime. When Regular insulin is injected before meals, a person must wait 30 to 60 minutes before eating. When lispro is used, no waiting is generally required before eating.

As an alternative to multiple injections, some people control their blood glucose with an insulin pump, which infuses insulin around the clock, just like a healthy pancreas, and allows a person to give extra insulin at meals.

This column is edited by Robert S. Dinsmoor, a Contributing Editor of Diabetes Self-Management.

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